Résumé
We previously reported that the inositol phosphates (IPs) synthesis is induced by muscarinic agonists in the rat cochlea and that this stimulation is maximal at postnatal day 12. This peak response is concomitant with the onset of the efferent synaptogenesis at the outer hair cell level. Whether the correlation between this neuronal plasticity and the enhanced IPs formation is unique to the rat or a general feature of the developing vertebrate cochlea is not known. To examine this question, we measured, in the presence of LiCI, the accumulation of (3H)-IPs induced by carbachol, in the developing chick cochlear duct during a period ranging from embryonic day (E) 8 to post-hatching day (P) 20. Carbachol (1 mM) causes a significant increase of IPs formation relative to basal values at all ages. This IPs accumulation is maximal at E8 (1854% of the basal level), then, rapidly decreases until P13 when it reaches a steady-state level of 294% of the basal level. Strikingly, this gradual decline in IPs formation is interrupted between El5 and El9, by a transient increase in IPs synthesis. This rise peaks at El6 with a stimulation value of 757% of the control level. This maximal stimulation is inhibited by atropine in a dose-dependent manner, as is the case at E9, suggesting the involvement of muscarinic receptors. Interestingly, the occurrence of the peak response is concomitant with the plastic events associated with the maturation of the efferent innervation of the cochlear duct. Thus, these results suggest that there may be a correlation between cochlear plasticity and enhanced IPs synthesis, which is not species-specific. The possible significance of the overall decrease in IPs formation, occurring during embryonic development , is discussed. The degradation of membrane phosphatidylinositol 4,5 biphosphate, by the enzyme phospholi-pase C, leads to the formation of diacylglycerol and inositol phosphates (IPs). Among these metabolites, diacylglycerol and inositol 1,4,5-trisphosphate are considered as second messengers. 4 The former directly activates the protein kinase C enzymes; the latter elicits a massive release of calcium from intracellular stores. This transduction system has been found to be driven by specific agonist-activated receptors such as muscarinic cholinergic receptors. 7 We previously reported that this transduction system is stimulated, in the rat cochlea, by muscarinic cholinergic agonists probably, via the activation of a M3 muscarinic receptor, s During the postnatal development of the mammalian cochlea, the muscarinic agonist-induced IPs formation is characterized by a peak around postnatal day 12. 3 This peak coincides with a time period during which plastic events lead to the setting up of the mature efferent innervation of the outer hair cells of the organ of Corti. I1 These efferent terminals are thought to be cholinergic. 6 Thus, it is conceivable that the IPs metabolism may play a role in cochlear neural plasticity. Whether this concomitance, between the increased IPs synthesis and the efferent synaptogenesis, is an overall developmental process in the vertebrate inner ear or is a specific feature of the rat cochlea remains to be investigated. To address this question, we studied the pattern of the phosphoinositide breakdown during the development of the chick basiler papilla. Although phylogenetically remote, the avian basilar papilla and the mammalian organ of Corti share some morphological homologies. They both possess, for instance, two types of hair cells lying on a basilar membrane and covered by a tector-ial membrane. The sensory hair cells are innervated, in both classes, by four different types of fibres, two of them belonging to the efferent systems and the other two to the efferent systems. II'16'23'25 Finally, physiological evidence, supporting the possibility of the presence of muscarinic receptors in the chick auditory organ, as this is the case in the rat cochlea, 3,8 is